Using the well-studied two-stage model of skin carcinogenesis, the first transgenic mouse with targeted expression of a polyamine metabolic enzyme was generated 30 years ago. Ornithine decarboxylase (ODC), a key regulating enzyme of polyamine biosynthesis, was constitutively expressed in the outer root sheath cells of hair follicles near the bulge stem cell niche using a keratin 6 promoter in K6/ODC mice. Early studies using K6/ODC mice demonstrated that polyamines play an essential role in the early promotional phase of skin tumorigenesis. Treatment with inhibitors of ODC activity blocked the formation of skin tumors and caused the rapid regression of existing tumors. We review how use of the K6/ODC mouse has shown that elevated polyamines in epithelial cells stimulate proliferation and invasiveness, recruit stem cells, alter chromatin remodeling and cell signaling leading to metabolic reprogramming, increase vascularization, activate underlying fibroblasts, and have powerful effects on immune cell function, all contributing to the development and progression of tumors.
Susan K. Gilmour (Thu,) studied this question.